POS0223 AMYLOID BURDEN AND ASSOCIATED FACTORS PREDICT HIGHER MORTALITY AND POOR OUTCOME IN FAMILIAL MEDITERRANEAN FEVER-ASSOCIATED AA AMYLOIDOSIS: DATA FROM A TERTIARY REFERRAL AMYLOIDOSIS CENTER WITH 137 PATIENTS
Authors: M. Bektaş, N. Koca, E. Oguz, B. Ince, S. Sari, N. Şentürk, Y. Yalçinkaya, B. Artim-Esen, M. Inanc, A. Gül
Journal: Annals of the Rheumatic Diseases (2022)

Background AA amyloidosis (AA-a) is a rare condition while the most common cause is Familial Mediterranean Fever (FMF) in Turkey. There is limited evidence about the impact of AA-a burden on prognosis and outcome in AA-a. Objectives We herein aimed to evaluate the AA-a burden and its association with outcome in patients (pts) with FMF-associated AA-a (FMF-AA) Methods We retrospectively evaluated FMF-AA pts from our AA-a cohort. Diagnosis of AA-a was confirmed by histologically. Heart involvement (inv.) was defined by documenting increased (&gt;12 mm) septal wall thickness (CSWT) and at least one of three appropriate echocardiography findings (decreased ejection fraction, increased granular echogenicity or valvulopathy, diastolic dysfunction). The pts were divided in three groups according to AA-a burden: pts had only renal inv. (Group 1, G1), renal and gastrointestinal (GIS) (Group 2, G2); renal and GIS and heart (Group 3, G3) Results Data of 137 pts with FMF-AA (55% male) were analyzed. We classified 79 pts in G1, 20 in G2, and 14 in G3. CSWT, troponin (trop) and pro-BNP levels were higher in G3 than G1 and G2 but trop levels were not statistically (sts) significant (sig.) between G3 and G2. Overall mortality was in 15.3 %. While mortality rate increased gradually with higher AA-a burden (10 % in G1, 15 % in G2 and 43 % in G3), the difference was sts sig. between G3 and G1. The number of MEFV variants was lower in pts with higher AA-a burden, especially those with M694V homozygosity were 93% and 72% in G1, 83% and 67% in G2, and 75% and 50% in G3 rsp; but the differences were not sts sig. (p=0.2 and p=0.7 for G1-G2, p=0.06 and p=0.2 for G1-G3, p=0.6 and p=0.4 for G2-G3). The number of organ inv. was correlated with CSWT (r=0.559’ ‘p&lt;0.001), trop (r=0.646’), pro-BNP (r=0.572’), bsl creatinine (Cre) (r=0.511’), bsl proteinuria (prt) levels (r=0.321 p=0.008) and negatively correlated with bsl e-GFR (r=-0.437’) and biologic DMARD duration (r=-0.235 p=0.03) ROC analyses revealed 56% sensitivity (SS) and 70 % specificity (SP) for bsl Cre (cut off value [COV] 0.95, AUC=0.726 p=0.03 95% CI 0.56-0.9), 83.3 % SS and 74 % SP for trop (COV 35.5 AUC=0.864 p=0.006 CI 0.73-0.99), 100 % SS and 85.5 % SP for pro-BNP (COV 7246 AUC=0.897 p=0.024 CI 0.79-1.0), 79% SS and 58 % SP for CSWT (COV 11.5 AUC=727 p=0.007 CI 0.61-0.84) to be able to predict higher mortality. Conclusion This study showed the association of AA-a burden with higher morbidity such as ESRD and higher mortality in pts with FMF-AA. Bsl Cre, prt, trop and pro-BNP levels were correlated with extent of AA-a burden and predicted higher mortality. Lower frequency of pts with two exon 10 variants or M694V homozygosity in pts with higher AA-a burden indicates that additional genetic and environmental factors may play a role in the development and progression of AA-a in FMF. Table 1. Clinical and laboratory features of pts with FMF-AA according to AA-a burden Variables G1 (n=79) G2 (n=20) G3 (n=14) p1 (OR) p2 p3 Age * Ɨ 42.8±13 43.2±13 48.9±11 0.9 0.1 0.2 Gender, male** 36 (45.6) 15 (75) 7 (50) 0.02 (5.5 ) 0.8 0.1 Diagnosis age of AA-a * Ɨ 30.7±13 34.1±14 34.9±15 0.3 0.3 0.9 Duration of AA-a * Ɨ 13.8±9 10.8±6 14.3±8 0.15 0.8 0.2 Baseline CRP (mg/L) Ɨ 20±13 24±19 13±7 0.4 0.05 0.07 Prt (g/dL) Ɨ Ɨ 3.8 (5.8) 12.4 (16) 5 (4.2) 0.03 0.3 0.2 Cre (mg/dL) Ɨ 0.8±0.4 1.5±1 1.8±1.3 &lt;0.001 &lt;0.001 0.6 e-GFR Ɨ# 104±31 104±31 59±39 0.02 0.004 0.5 CRF at admission** 28/74 (38) 13/19 (68) 9/12 (75) 0.02 (5.7 ) 0.03 (6 ) 0.7 ESRD at admission** 7/62 (11) 6/18 (33) 4/11 (36) 0.03 (5 ) 0.03 (4.6 ) 0.9 CSWT Ɨ 10.2±1.7 10.6±1.1 13.9±1.6 0.3 &lt;0.001 &lt;0.001 Trop ĸ Ɨ Ɨ 9 (13) 28 (68) 75 (85) 0.4 0.005 0.1 pro-BNP ĸ Ɨ Ɨ 288 (1040) 766 (1967) 4968 (33800) 0.5 0.003 0.026 ESRD (overall)** 35 (45) 10 (50) 13 (93) 0.7 0.001 (11 ) 0.01 (7 ) Duration of b-DMARD (months) Ɨ## 66±29 67.7±37 41.8±30 0.9 0.02 0.08 Mortality ** 8 (10) 3 (15) 6 (43) 0.5 0.006 (10 ) 0.1 #estimated glomerular filtration rate p1: G2-G1 p2: G3-G1 p3: G2-G3 Ɨ mean±std dev. Ɨ Ɨ median (IQR) *years ** n, % ĸ pg/mL Figure 1. Comparison of survival rate between G3 and G1 Log-Rank: p=0.007 Disclosure of Interests None declared